Concurrent oncogene mutation profile in Chinese patients with stage Ib lung adenocarcinoma.
Concurrent oncogene mutation profile in Chinese patients with stage Ib lung adenocarcinoma.
复制标题
DOI：
10.1097/md.0000000000000296
复制
发表时间：
2014-12
期刊：
影响因子：
1.6
通讯作者：
Zhang LJ
中科院分区：
文献类型：
--
作者：
Wen YS;Cai L;Zhang XW;Zhu JF;Zhang ZC;Shao JY;Zhang LJ
肺癌的分子特征与癌变、对靶向治疗的反应和预后有关。随着并发癌基因突变的报道越来越多，基于驱动基因突变的治疗调整将改善治疗。我们拟研究中国人群中Ib期肺腺癌并发癌基因突变的分布，并找出中国人群中EGFR和KRAS中最常突变基因与生存结局的相关性。同时，我们试图通过实时荧光鉴定反转录聚合酶链反应（RT-PCR）验证Sequenom方法在癌基因检测中的应用。本文回顾性分析了1999年至2007年间在我院接受手术切除的156例患者。利用飞行时间质谱法检测了19个癌基因的238个突变热点。156例患者中有86例（55.13%）发生基因突变。EGFR是最常见的驱动突变基因，发生率为44.23%，其次是KRAS（8.33%）、PIK3CA（3.84%）、KIT（3.20%）、BRAF（2.56%）、AKT（1.28%）、MET（0.64%）、NRAS（0.64%）、HRAS（0.64%）和ERBB2（0.64%）。RET、PDGFRA、FGFR1、FGFR3、FLT3、ABL、CDK或JAK2癌基因未发现突变。多基因突变13例（8.3%）。除EGFR和KRAS突变外，6例患者还存在PIK3CA突变。EGFR突变可与NRAS、KIT、ERBB2和BRAF突变共存。仅有1例患者发现KRAS突变与EGFR T790M突变共存。否则，EGFR和KRAS的突变似乎是相互排斥的。EGFR/KRAS突变对生存没有好处。在我们的研究中观察到几个伴随的驱动基因突变。EFGR/KRAS突变未被证实为预后因素。RT-PCR验证了飞行时间质谱法检测多基因突变的有效性，是检测多基因突变的另一种选择，可广泛应用于临床实践，有助于指导治疗。
Supplemental Digital Content is available in the text Molecular characteristics in lung cancer are associated with carcinogenesis, response to targeted therapies, and prognosis. With concurrent oncogene mutations being reported more often, the adjustment of treatment based on the driver gene mutations would improve therapy. We proposed to investigate the distribution of concurrent oncogene mutations in stage Ib lung adenocarcinoma in a Chinese population and find out the correlation between survival outcome and the most frequently mutated genes in EGFR and KRAS in Chinese population. Simultaneously, we tried to validate the Sequenom method by real time fluoresce qualification reverse transcription polymerase chain reaction (RT-PCR) in oncogene detection. One hundred fifty-six patients who underwent complete surgical resection in our hospital between 1999 and 2007 were retrospectively investigated. Using time-of-flight mass spectrometry, 238 mutation hotspots in 19 oncogenes were examined. Genetic mutations occurred in 86 of 156 patients (55.13%). EGFR was most frequently gene contained driver mutations, with a rate of 44.23%, followed by KRAS (8.33%), PIK3CA (3.84%), KIT (3.20%), BRAF (2.56%), AKT (1.28%), MET (0.64%), NRAS (0.64%), HRAS (0.64%), and ERBB2 (0.64%). No mutations were found in the RET, PDGFRA, FGFR1, FGFR3, FLT3, ABL, CDK, or JAK2 oncogenes. Thirteen patients (8.3%) were detected in multiple gene mutations. Six patients had PIK3CA mutations in addition to mutations in EGFR and KRAS. EGFR mutations can coexist with mutations in NRAS, KIT, ERBB2, and BRAF. Only one case was found to have a KRAS mutation coexisting with the EGFR T790M mutation. Otherwise, mutations in EGFR and KRAS seem to be mutually exclusive. There is no survival benefit in favor of EGFR/KRAS mutation. Several concomitant driver gene mutations were observed in our study. None of EFGR/KRAS mutation was demonstrated as a prognostic factor. Polygenic mutation testing by time-of-flight mass spectrometry was validated by RT-PCR, which can be an alternative option to test for multiple mutations and can be widely applied to clinical practice and help to guide treatment.